The human CD83 gene is located on chromosome 6p23 and composed of five exons and four introns spanning over a total length of 19.284 kb (Berchtold, S. et al., Ann. Hum. Genet. 63:181-183 (1999)). Likewise, the murine CD83 gene spans over a total length of ˜19 kb, consisting of five exons and four introns, although it is located on chromosome 13 band A 5. CD83 is expressed in most, if not all, vertebrate species. It has been reported to be expressed by humans, chimpanzee, horse, swine, cattle, panda, dog, rat, mouse, frog, elasmobranch and teleost fish, sharing the highest amino acids (aa) sequence homology with chimpanzee (pan troglodytes, 99%), horse, (equus caballus, 76%), cattle (bos taurus, 74%), swine (sus scrofa, 72%) and mouse (mus musculus, 65%) and to a lesser extend with fish (oncorhynchus mykiss and ginglymostoma cirratum, 28% and 32% respectively) (Lechmann, M. et al., Biochem. Biophys. Res. Commun. 329:132-139 (2005); Ohta, Y. et al. J. Immunol. 173:4553-4560 (2004)).
The human minimal CD83 promoter sequence was disclosed in Berchtold, S. et al. Immunobiology 205:231-246(2002). A 3037 bp long fragment upstream of the transcription start codon has been cloned and used to narrow the core promoter sequence down to 261 bp. By bioinformatical analyses four specificity protein 1 (SP-1) and one NFκB-binding element were identified and could verified by electrophoretic mobility shift assays (EMSA). These findings are in concordance with those from other groups: McKinsey and colleagues described that NFκB regulates inducible CD83 gene expression in activated T lymphocytes (McKinsey, T. A. et al., Mol. Immunol. 37:783-788 (2000)) and Dudziak and co-workers published that Epstein Barr virus' latent membrane protein 1 (LMP1) induces CD83 expression in B cells via the NFκB-signalling pathway (Dudziak, D. et al., J. Virol. 77:8290-8298 (2003)). Interestingly, Berchtold and co-workers found similar activity of the 261 bp CD83 minimal promoter in several other cell types than DCs. This minimal promoter displayed activity in mature human moDCs, but also in the human monocyte cell line U937 as well as in human leukaemia Jurkat T cells (both expressing CD83) and in the murine DC-like cell line DC2.4.
The exact promoter sequence of the murine CD83 has not been identified yet, but consistent with the human CD83 promoter region, the murine 5′ region of the CD83 gene lacks a clear TATA box sequence. However, no conservation of specific transcription factor binding sequences between mice and human were found yet in the minimal promoter region (Twist, C. J. et al., Immunogenetics 48:383-393 (1998)).
In summary, the human 261 bp CD83 minimal promoter showed neither cell type nor maturation specific activity for DCs. This leads to the conclusion that additional regulatory elements must be involved in the cell type- and stadium-specific regulation of the human CD83 gene expression, which have not been identified yet (Ilka Knippertz, I., Thesis Universität Erlangen-Nueremberg, 91-98. Jan. 7, 2008).